**1. Introduction**

182 New Approaches to the Study of Marine Mammals

sirenias and otters. Pp. 531

*Lobos y Lobos Marinos* No. 4, pp. 12

NMFS 51. Cambridge, 23-27 April 1984.

113, No. 2 (September, 1981), pp. 712–724

*Diseases*, Vol. 31, No.1, (January, 1995), pp. 83-86

pp. 152–179

Philadelphia, PA

Monaco, (January 1998), pp. 153

(May, 1999), pp. 2519-2526

Vaz-Ferreira, R. (1982). *Arctocephalus australis* (Zimmermann), South American fur seal. Pp. 497-508. In: *Mammals in the Seas*. FAO Fisheries Series 5, Vol. 4. Small cetaceans, seals,

Vaz-Ferreira, R. & Achaval, F. (1979). Relación y reconocimiento materno-filial en *Otaria flavescens* (Shaw) "lobo de un pelo" y reacciones de los machos subadultos ante los

Vaz-Ferreira, R. & Palerm, E. (1962). Efectos de los cambios meteorológicos sobre agrupaciones terrestres de Pinnipedios. Ministerio de Industrias y Trabajo. Servicio Oceanográfico y de Pesca. Departamento Científico y Técnico. *Trabajos sobre Islas de* 

Vaz-Ferreira, R. & Sierra de Soriano, B. (1962). Estructura de una agrupación social reproductora de *Otaria byronia* (de Blainville), representación gráfica. Ministerio de Industrias y Trabajo. Servicio Oceanográfico y de Pesca. Departamento Científico y

Vaz-Ferreira, R. & Ponce de León, A. (1984). Estudios sobre *Arctocephalus australis* (Zimmermann, 1783), lobo de dos pelos sudamericano, en Uruguay. Facultad de Humanidades y Ciencias, Universidad de la República. Contribuciones del

Vaz-Ferreira, R. & Ponce de León, A. (1987). South American Fur Seal, *Arctocephalus australis*, in Uruguay. Pp 29-32 In: *Proceedings of an International Symposium and Workshop.* Status, biology and ecology of fur seals. Croxall & Gentry. (Editors). NOAA Technical Report

Webster, R. G.; Hinshaw, V. S.; Bean, W. J.; Van Wyke, K. L.; Geraci, J. R.; St Aubin, D. J. & Petursson, G. (1981). Characterization of an influenza A virus from seals. *Virology*. Vol.

Webster, R. G.; Bean, W. J.; Gorman, O. T.; Chambers, T. M. & Kawaoka Y. (1992). Evolution and ecology of Influenza A viruses. *Microbiology Reviews*, Vol. 56, No.1 (March, 1992),

Woods, R.; Cousins, D. V.; Kirkwood, R. & Obendorf D.L. (1995). Tuberculosis in a wild Australian fur seal (*Arctocephalus pusillus doriferus*) from Tasmania. *Journal of Wildlife* 

Wright, P., & Webster, R .G. (2001). Orthomyxoviruses. In: *Fields virology*. B. N. Fields, D. M. Knipe and P. M. Howley, Eds. pp 1254–1292. Lippincott-Raven Publishers,

York. A.; Lima, M.; Ponce de León, A.; Malek, A. & Páez, E. (1998). First description of diving females South American fur seals in Uruguay. Abstract Volume. *WMMSC*,

Zumárraga, M. J.; Bernardelli, A.; Bastida, R.; Quse, V.; Loureiro, J.; Cataldi, A.; Bigi, F.; Alito, A.; Castro Ramos, M.; Samper, S.; Otal, I.; Martin, C. & Romano, M. I. (1999). Molecular characterization of mycobacteria isolated from seals. *Microbiology*, Vol. 145,

Departamento de Oceanografía. Montevideo, Uruguay. Vol. 1, No. 8, pp. 1-18 Vaz-Ferreira, R. & Ponce de León, A. (1985). Estructura de grupos de dos especies de

cachorros. *Acta Zoologica Lilloana*, Vol. 35, (1979), pp. 295-302

Técnico. *Trabajos sobre Islas de Lobos y Lobos Marinos,* No. 3, pp. 12

Otariidae. *Actas de las Jornadas de Zoología de Uruguay*, pp. 75-77

Incidences of infectious diseases in marine mammals have been increasing [1]. Among them, morbillivirus infection is the greatest threat to marine mammals becuase it has caused mass die-offs in several pinniped and cetacean species in the past few decades [2,3]. The genus *Morbillivirus* belongs to the family Paramyxoviridae, and the viruses in this genus have a genome consisting of a single piece of negative-stranded RNA, which encodes eight viral proteins: a nucleocapsid protein (N); a phosphoprotein (P); two virulence factors (C and V); a matrix protein (M); a membrane fusion protein (F); a hemagglutinin binding protein (H); and an RNA polymerase (L) [4]. The two viral surface glycoproteins, H and F, play important roles during the viral infection of host cells. The H protein is required for viral attachment to the host cells, while the F protein mediates membrane fusion with the host plasma membrane and enables the entry of the virus.

Until the discovery of a new mobillivirus in marine mammals in 1988, only four morbillivirus species had been identified in land mammals: the measles virus (MV); rinderpest virus (RPV); peste des petits ruminants virus (PPRV); and canine distemper virus (CDV) [4]. The new morbillivirus was isolated from dead harbor seals (*Phoca vitulina*) in a mass die-off around the Baltic and North Sea coasts and was named phocine distemper virus (PDV) [5,6]. Two other new viruses originating in cetaceans were also isolated from dead harbor porpoises (*Phocoena phocoena*) and striped dolphins (*Stenella coeruleoalba*) and were named porpoise morbillivirus (PMV) and dolphin morbillivirus (DMV) [7,8]. Based on the similarities of the gene sequences, it was proposed that the cetacean-origin viruses be unified as a single species, cetacean morbillivirus (CMV) [9,10].

© 2012 Ohishi et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Morbilliviruses propagate primarily in lymphoid tissues and induce acute disease. They are usually accompanied by lymphopenia and immunosuppression, which often lead to secondary, opportunistic infections in the host. The distemper viruses, CDV and PDV, often invade the central nervous systems of their hosts, although acute encephalitis is not common in other morbillivirus infections [4]. A notable feature of morbilliviruses is their high host specificity. The natural host of MV is humans, but it can also infect monkeys. Ruminants are the targets of RPV and PPRV. RPV mainly infects cattle, while PPRV infects goats and sheep. Although these viruses have multiple host compatibilities, they induce more severe disease in the primary hosts than in others [11,12]. The natural host for CDV is dogs, but ferrets (*Mustela putorius furo*) have been used as an experimental model due to their high sensitivity to CDV. Recently, the host range of CDV has been shown to be wider than previously thought and expanded to include other wild carnivores, such as Baikal seals (*Phoca sibirica*) or lions (*Panthera leo*) [13-15]. PDV and CMV have been isolated only from seals and cetaceans, respectively. While no morbilliviruses have been isolated from sirenians, serologic evidence of exposure to morbillivirus was reported in manatees (*Trichechus manatus*) without showing clinical signs of disease [16,17].

Host-Virus Specificity of the Morbillivirus Receptor, SLAM, in Marine Mammals:

inhabiting the same locales [25,26]. About the same time as the first outbreak on northern European coasts, in 1987–1988 the deaths of approximately 18,000 Baikal seals were reported in Lake Baikal which showed clinical signs identical to those reported in European seals [13]. However, subsequent genomic characterization revealed that the cause of the mass dieoff of Baikal seals was CDV [27-31]. CDV also induced another mass die-off among Caspian seals (*Phoca caspica*), in which many seals died in 1997 and 2000, near Azerbaijan on the

Date Site Animal species No. of dead Virus 1987-1988 USA Atlantic coast *Tursiops truncatus* >2,500 CMV 1987-1988 Lake Baikal *Phoca sibirica* >18,000 CDV 1988 North & Baltic Sea *Phoca vitulina* >18,000 PDV 1990 Mediterrean Sea *Stenella coeruleoalba* >2,000 CMV 1993 Mexican Gulf *Tursiops truncatus* >1,000 CMV 1997 Caspian Sea *Phoca caspica* >2,000 CDV 2000 Caspian Sea *Phoca caspica* >10,000 CDV 2002 North & Baltic Sea *Phoca vitulina* >21,000 PDV

The first evidence of morbillivirus infection in cetaceans was described in several stranded harbor porpoises with pathological changes on the Irish coastline in 1988 [7]. A new morbillivirus was isolated and termed PMV for "porpoise" [34]. Since 1990, a severe mass die-off began to affect the striped dolphin (*Stenella coeruleoalba*) population on the Mediterranean coast of Spain and rapidly spread throughout the western Mediterranean Sea, including the coasts of France, Italy, Greece, and Turkey [8,35] (Table 1). A new virus, named DMV for "dolphin" was isolated as the causative agent [9]. A retrospective serologic investigation indicated that PMV and DMV were the agents responsible for another epidemic in bottlenose dolphins (*Tursiops truncatus*) along the Atlantic coast of the USA, for which the causative agent had been initially thought to be brevetoxin produced by a marine dinoflagellate (*Ptychodiscus brevis*) [36-38]. PMV also induced a die-off of bottlenose dolphins in the Gulf of Mexico during 1993–1994 [37-39]. Molecular biological analyses of these cetacean morbilliviruses showed that their gene sequences were similar [9,10]. Based on the similarities, it was proposed that these cetacean morbilliviruses be classified as a single

Thus, morbillivirus infection has a strong impact on populations of marine mammals, as listed in Table 1. In addition to mass die-offs, many smaller-scale die-offs were reported in various oceans. Even if the scale is small, outbreaks of morbillivirus infection can have serious consequences for marine mammal populations, especially among endangered species at risk of extinction, such as Mediterranean monk seals (*Monachus monachus*). In 1997, approximately 50% of the population of Mediterranean monk seals residing along the

CMV, cetacean morbillivirus; CDV, canine distemper virus; PDV, phocine distemper virus.

**Table 1.** Mass die-offs of marine mammals caused by morbilliviruses.

western shores of the Caspian Sea [32,33].

species called CMV.

Risk Assessment of Infection Based on Three-Dimensional Models 185

The cellular receptor of a virus is one of the major determinants of host specificity and tissue tropism. The signaling lymphocyte activation molecule (SLAM) has recently been shown to be the principal cellular receptor for morbilliviruses in humans, cows, and dogs [18,19]. SLAM itself was first discovered in 1995 as a novel receptor molecule involved in T-cell activation [20]. It is expressed on various immune cells, such as thymocytes, activated T and B cells, mature dendritic cells, macrophages, and platelets [21,22]. SLAM is also a marker for the most primitive hematopoetic stem cells [23]. The distribution and function of SLAM are consistent with the cell tropism and immunosuppressive nature of morbilliviruses. This indicates that the host range of morbillivirus may be explained by key amino acid residues of SLAM on the interface with morbillivirus.

In this chapter, we review morbillivirus infection in marine mammals and its possible primary receptor in the host, SLAM. Further, we discuss host–virus specificities based on three-dimensional models of SLAM and risk assessment of morbillivirus infection in marine mammals.
